Antigiardial Activity of Acetylsalicylic Acid Is Associated with Overexpression of HSP70 and Membrane Transporters

Giardia lamblia is a flagellated protozoan responsible for giardiasis, a worldwide diarrheal disease. The adverse effects of the pharmacological treatments and the appearance of drug resistance have increased the rate of therapeutic failures. In the search for alternative therapeutics, drug repositioning has become a popular strategy. Acetylsalicylic acid (ASA) exhibits diverse biological activities through multiple mechanisms. However, the full spectrum of its activities is incompletely understood. In this study we show that ASA displayed direct antigiardial activity and affected the adhesion and growth of trophozoites in a time-dose-dependent manner. Electron microscopy images revealed remarkable morphological alterations in the membrane, ventral disk, and caudal region. Using mass spectrometry and real-time quantitative reverse transcription (qRT-PCR), we identified that ASA induced the overexpression of heat shock protein 70 (HSP70). ASA also showed a significant increase of five ATP-binding cassette (ABC) transporters (giABC, giABCP, giMDRP, giMRPL and giMDRAP1). Additionally, we found low toxicity on Caco-2 cells. Taken together, these results suggest an important role of HSPs and ABC drug transporters in contributing to stress tolerance and protecting cells from ASA-induced stress.

Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds

Giardiasis is a diarrheal disease that is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; however, failures in drug therapy are common, and have adverse effects and increased resistance of the parasite to the drug, generating the need to find new alternative treatments. In this study, we synthesized a series of 2-mercaptobenzimidazoles that are derivatives of omeprazole, and the chemical structures were confirmed through mass, 1H NMR, and 13C NMR techniques. The in vitro efficacy compounds against Giardia, as well as its effect on the inhibition of triosephosphate isomerase (TPI) recombinant, were investigated, the inactivation assays were performed with 0.2 mg/mL of the enzyme incubating for 2 h at 37 °C in TE buffer, pH 7.4 with increasing concentrations of the compounds. Among the target compounds, H-BZM2, O2N-BZM7, and O2N-BZM9 had greater antigiardial activity (IC50: 36, 14, and 17 µM on trophozoites), and inhibited the TPI enzyme (K2: 2.3, 3.2, and 2.8 M−1 s−1) respectively, loading alterations on the secondary structure, global stability, and tertiary structure of the TPI protein. Finally, we demonstrated that it had low toxicity on Caco-2 and HT29 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.

Anti-Protozoal Potential of Heterocyclic Compounds Against Giardiasis

The aim of this literature review is to compile data of heterocyclic antigiardial agents. The importance is to analyze the structural requirements for improved antigiardial activity, to overcome resistance and enhance the bioavailability of the compounds under study. Though, nitroimidazoles/ imidazoles and benzimidazoles are major classes, other heterocyclic scaffolds viz. oxoindolinylidene, dioxodihydroisobenzofuran-5-carboxamide, fluoroquinolone, thieno[2,3-b]pyridine- 5-carbonitrile, α-amino-phosphonate analogs of polyoxins, nitazoxanide benzologue, thiazole and triazolyl- quinolone chalcone also possess activity against Giardia species. Heterocyclic phytoconstituents are also included to have a deep idea of antigiardial activity of herbs possessing heterocyclic constituents.

Antigiardial Activity of Cupania dentata Bark and its Constituents

The MeOH extract of <em>Cupania dentata</em> bark (Sapindaceae) as well as its hexane, CH₂Cl₂, EtOAc, and BuOH fractions showed high activity against <em>Giardia lamblia</em> trophozoites (IC₅₀ = 2.12-9.52 μg/mL). The phytochemical study of fractions resulted in the isolation of taraxerone (<strong>1</strong>), taraxerol (<strong>2</strong>), scopoletin (<strong>3</strong>), and two mixtures of steroidal compounds. Taraxerone was the metabolite with the highest giardicidal activity (IC₅₀ = 11.33 μg/mL).